Pathologic changes in mice induced by subtilase cytotoxin, a potent new Escherichia coli AB(5) toxin that targets the endoplasmic reticulum

Subtilase cytotoxin (SubAB) is the prototype of a recently discovered AB₅ cytotoxin family produced by certain strains of Shiga toxigenic Escherichia coli (STEC). The catalytic A subunit is a highly specific subtilase-like serine protease that cleaves the endoplasmic reticulum chaperone BiP. The toxin is lethal for mice, but the pathology it induces is poorly understood. Here, we show that intraperitoneal injection of SubAB causes microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment in mice-characteristics typical of Shiga toxin-induced hemolytic uremic syndrome. SubAB caused extensive microvascular thrombosis and other histologic damage in the brain, kidneys, and liver, as well as dramatic splenic atrophy. Peripheral blood leukocyte levels were increased at 24 h; there was also significant neutrophil infiltration in the liver, kidneys, and spleen and toxin-induced apoptosis at these sites. These findings raise the possibility that SubAB directly contributes to pathology in humans infected with strains of STEC that produce both Shiga toxin and SubAB.Hui Wang, James C. Paton, and Adrienne W. Pato

Gluelump Spectrum in the Bag Model

We explore the ordering of the lowest levels in a simple bag model of the ``gluelump'' of Michael and also discuss, again within the context of the bag model, the related problem of hybrid potentials in the limit of very small spacing between quark and anti-quark sources.Comment: 10 page

Chandra X-Ray Spectroscopy Of The Very Early O Supergiant HD 93129A: Constraints On Wind Shocks And The Mass-Loss Rate

We present an analysis of both the resolved X-ray emission-line profiles and the broad-band X-ray spectrum of the O-2 If* star HD 93129A, measured with the Chandra High Energy Transmission Grating Spectrometer ( HETGS). This star is among the earliest and most massive stars in the Galaxy, and provides a test of the embedded wind-shock scenario in a very dense and powerful wind. A major new result is that continuum absorption by the dense wind is the primary cause of the hardness of the observed X-ray spectrum, while intrinsically hard emission from colliding wind shocks contributes less than 10 per cent of the X-ray flux. We find results consistent with the predictions of numerical simulations of the line-driving instability, including line broadening indicating an onset radius of X-ray emission of several tenths of R-*. Helium-like forbidden-to-intercombination line ratios are consistent with this onset radius, and inconsistent with being formed in a wind-collision interface with the star\u27s closest visual companion at a distance of 100 au. The broad-band X-ray spectrum is fitted with a dominant emission temperature of just kT = 0.6 keV along with significant wind absorption. The broad-band wind absorption and the line profiles provide two independent measurements of the wind mass-loss rate:. M = 5.2(-1.5)(+1.8) x 10(-6) and 6.8(-2.2)(+2.8) x 10(-6) M-circle dot yr(-1), respectively. This is the first consistent modelling of the X-ray line-profile shapes and broad-band X-ray spectral energy distribution in a massive star, and represents a reduction of a factor of 3-4 compared to the standard H alpha mass-loss rate that assumes a smooth wind

Undergraduate teaching in geriatric medicine: mapping the British Geriatrics Society undergraduate curriculum to Tomorrow's Doctors 2009

Introduction: in 2008, the British Geriatrics Society (BGS) developed the Recommended Undergraduate Curriculum in Geriatric Medicine. This was subsequently mapped to the second edition of Tomorrows' Doctors (TD2, 2003). Following the publication of the third edition of Tomorrow's Doctors in 2009 (TD3), the mapping exercise was repeated to verify the extent to which the updated General Medical Council recommendations supported teaching in ageing and geriatric medicine. Method: we analysed TD3 and identified 48 aspects of its general guidance that were relevant to the teaching of medicine for older people. We then mapped these to the 2009 BGS curriculum. Results: the BGS curriculum was supported in full by TD3. However, learning outcomes relating to the interpretation and conduct of research in TD3 had no corresponding outcomes in the BGS curriculum. Conclusion: the BGS curriculum for medical undergraduates continues to provide a specific and complete list of learning objectives, all of which could help to operationalise the general statements made in TD3 with relation to ageing and geriatric medicine. Learning outcomes in research in frail older patients have been added following this mapping exercise

Individual-Based Modelling of Bacterial Ecologies and Evolution

This paper presents two approaches to the individual-based modelling of bacterial ecologies and evolution using computational tools. The first approach is a fine-grained model that is based on networks of interactivity between computational objects representing genes and proteins. The second approach is a coarser-grained, agent-based model, which is designed to explore the evolvability of adaptive behavioural strategies in artificial bacteria represented by learning classifier systems. The structure and implementation of these computational models is discussed, and some results from simulation experiments are presented. Finally, the potential applications of the proposed models to the solution of real-world computational problems, and their use in improving our understanding of the mechanisms of evolution, are briefly outlined

How to increase earthquake and home fire preparedness: the fix-it intervention

Published, evaluated community intervention studies concerning natural hazard preparedness are rare. Most lack a rigorous methodology, thereby hampering the development of evidence-based interventions. This paper describes the rationale and methodology of a cross-cultural, longitudinal intervention study on earthquake and home fire preparedness, termed fix-it. The aim is to evaluate whether and how the intervention brings about behaviour change in the targeted communities in two coastal cities with high seismic risk: Seattle, USA and Izmir, Turkey. Participants are adult residents of these cities. The intervention group attends a 6-h workshop, which focuses on securing items in the household. The control group does not attend the workshop. All participants complete baseline and post-intervention, as well as 3- and 12-month follow-up assessments. The primary outcome measure is an observational measure of nine preparedness items for earthquake and fire in participants’ homes. This is evaluated alongside participants’ self-reports concerning their preparedness levels. Secondary outcomes are changes in levels of self-efficacy, perceived outcome, trust, corruption, empowerment, anxiety and social cohesion. Results from the first of the studies, conducted in Seattle in September 2015, indicate that while the fix-it intervention is effective, in the longer term, multi-hazard preparedness is increased by the mere act of going into people’s homes to observe their preparedness levels along with assessing self-reported preparedness and sociopsychological orientation towards natural hazards. This protocol and study aim to augment the empirical literature on natural hazard preparedness, informing national and international policy on delivery of evidence-based community interventions to promote multi-hazard preparedness in households

Validity, practical utility, and reliability of the activPAL in preschool children

<p>Purpose: With the increasing global prevalence of childhood obesity, it is important to have appropriate measurement tools for investigating factors (e.g. sedentary time) contributing to positive energy balance in early childhood. For pre-school children, single unit monitors such as the activPALTM are promising. However, validation is required as activity patterns differ from adults.</p> <p>Methods: Thirty pre-school children participated in a validation study. Children were videoed for one hour undertaking usual nursery activity while wearing an activPALTM. Video (criterion method) was analyzed on a second-by-second basis to categorise posture and activity. This was compared with the corresponding activPALTM output. In a subsequent sub-study investigating practical utility and reliability, 20 children wore an activPALTM for seven consecutive 24-hour periods.</p> <p>Results: A total of 97,750 seconds of direct observation from 30 children were categorized as sit/lie (46%), stand (35%), walk (16%); with 3% of time in nonsit/lie/upright postures (e.g. crawl/crouch/kneel-up). Sensitivity for the overall total time matched seconds detected as activPALTM ‘sit/lie’ was 86.7%, specificity 97.1%, and positive predictive value (PPV) 96.3%. For individual children, the median (interquartile range) sensitivity for activPALTM sit/lie was 92.8% (76.1-97.4), specificity 97.3% (94.9-99.2), PPV 97.0% (91.5-99.1). The activPALTM underestimated total time spent sitting (mean difference -4.4%, p<0.01), and overestimated time standing (mean difference 7.1%, p<0.01). There was no difference in overall % time categorised as ‘walk’ (p=0.2). The monitors were well tolerated by children during a seven day period of free-living activity. In the reliability study, at least five days of monitoring were required to obtain an intraclass correlation coefficient of ≥0.8 for time spent sit/lie according to activPALTM output.</p> <p>Conclusion: The activPAL had acceptable validity, practical utility, and reliability for the measurement of posture and activity during freeliving activities in pre-school children.</p&gt